title: Convenient Synthesis and Evaluation of Heptadentate Bifunctional Ligand for Radioimmunotherapy Applications.
abstract: An efficient synthetic route to a bifunctional chelating agentC-NE3TA-NCS for antibody-targeted radioimmunotherapy (RIT) applications was developed. Various synthetic methods centered on the key reaction steps including bimolecular cyclization, ring opening reactions of aziridine and aziridinium cations, and reductive aminiation were explored to optimize the preparation of a tetraaza-based chelate TANPA andC-NE3TA analogues. HeptadentateC-NE3TA-NCS was conjugated to a tumor targeting antibody and compared to hexadentateC-NOTA-NCS for radiolabeling reaction kinetics with lanthanides for RIT.C-NE3TA-antibody conjugate displayed significantly enhanced complexation kinetics with90Y as compared toC-NOTA-antibody conjugate. The synthetic methods for TANPA andC-NE3TA-NCS reported herein have broad applications for preparation of bifunctioanl macrocyclic chelating agents.
authors.forename: Hyun-Soon
authors.initials: HS
authors.lastname: Chong
authors.forename: Xiang
authors.initials: X
authors.lastname: Sun
authors.forename: Pengfei
authors.initials: P
authors.lastname: Dong
authors.forename: Chi Soo
authors.initials: CS
authors.lastname: Kang
keywords: 90Y; Bifunctional chelating agent; Macrocyclic ligand; radioimmunotherapy